Ignite Creation Date:
2025-12-25 @ 1:05 AM
Ignite Modification Date:
2026-01-01 @ 7:46 AM
Study NCT ID:
NCT05616793
Status:
RECRUITING
Last Update Posted:
2025-12-19
First Post:
2022-11-07
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D012162', 'term': 'Retinal Degeneration'}], 'ancestors': [{'id': 'D015785', 'term': 'Eye Diseases, Hereditary'}, {'id': 'D005128', 'term': 'Eye Diseases'}, {'id': 'D012164', 'term': 'Retinal Diseases'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Enrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).\n\nConcurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 22}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2023-06-15', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-12', 'completionDateStruct': {'date': '2028-06-15', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-17', 'studyFirstSubmitDate': '2022-11-07', 'studyFirstSubmitQcDate': '2022-11-07', 'lastUpdatePostDateStruct': {'date': '2025-12-19', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2022-11-15', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2028-06-15', 'type': 'ESTIMATED'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'Microperimetry', 'timeFrame': '1 year', 'description': 'Mean sensitivity, in dB'}, {'measure': 'Kinetic perimetry', 'timeFrame': '1 year', 'description': 'Field extent, in degrees'}, {'measure': 'Virtual Reality Orientation and Mobility Test (VR-O&M)', 'timeFrame': '1 year', 'description': 'Performance over a range of light levels'}, {'measure': 'Frequency doubling technology (FDT) perimetry (sFDT-CA)', 'timeFrame': '1 year'}, {'measure': 'Light-adapted transient pupillary light reflex (LA-TPLR)', 'timeFrame': '1 year'}, {'measure': 'Sweep visual evoked potentials (sVEPs)', 'timeFrame': '1 year'}, {'measure': 'Chromatic referential looking', 'timeFrame': '1 year', 'description': 'In dark-adapted patients'}, {'measure': 'Full-field chromatic sensitivity testing (FST)', 'timeFrame': '1 year', 'description': 'In free view'}, {'measure': 'Portable chromatic pupillometry Portable chromatic pupillometry', 'timeFrame': '1 year'}], 'primaryOutcomes': [{'measure': 'Incidence of Dose Limiting Toxicities', 'timeFrame': '2 years', 'description': 'Number of DLT events'}, {'measure': 'Number of adverse events related to OPGx-001', 'timeFrame': '2 years', 'description': 'Number of AEs related to IP'}, {'measure': 'Incidence of adverse events related to OPGx-001', 'timeFrame': '2 years', 'description': 'Incidence of AEs related to IP'}, {'measure': 'Severity of adverse events related to OPGx-001', 'timeFrame': '2 years', 'description': 'Severity of AEs related to IP'}, {'measure': 'Number of procedure-related adverse events', 'timeFrame': '2 years', 'description': 'Number of AEs related to IP administration'}, {'measure': 'Incidence of procedure-related adverse events', 'timeFrame': '2 years', 'description': 'Incidence of AEs related to IP administration'}, {'measure': 'Severity of procedure-related adverse events', 'timeFrame': '2 years', 'description': 'Severity of AEs related to IP administration'}, {'measure': 'Assessment of cross-sectional spectral domain optical coherence tomography images', 'timeFrame': '2 years', 'description': 'Qualitative Assessment of SD-OCT image'}, {'measure': 'Assessment of Natural course of LCA5-IRD', 'timeFrame': '6 months', 'description': 'Change from baseline in MLoMT'}, {'measure': 'Assessment of Natural course of LCA5-IRD', 'timeFrame': '6 months', 'description': 'Change from baseline in FST'}, {'measure': 'Assessment of Natural course of LCA5-IRD', 'timeFrame': '6 months', 'description': 'Change from baseline in BCVA'}, {'measure': 'Assessment of Natural course of LCA5-IRD', 'timeFrame': '6 months', 'description': 'Change from baseline in FCP/Microperimetry'}, {'measure': 'Assessment of Natural course of LCA5-IRD', 'timeFrame': '6 months', 'description': 'Change from baseline in SD-OCT'}, {'measure': 'Assessment of Natural course of LCA5-IRD', 'timeFrame': '6 months', 'description': 'Change from baseline in pupillometry'}, {'measure': 'Assessment of Natural course of LCA5-IRD', 'timeFrame': '6 months', 'description': 'Number of adverse events'}], 'secondaryOutcomes': [{'measure': 'Change from baseline over time in Multi-luminance Orientation and Mobility Test', 'timeFrame': '2 years', 'description': 'Number of objects identified'}, {'measure': 'Change from baseline over time in Dark-adapted full-field sensitivity testing', 'timeFrame': '2 years', 'description': 'FST'}, {'measure': 'Change from baseline over time in best corrected visual acuity (BCVA)', 'timeFrame': '2 years', 'description': 'Measured using LogMAR scale'}, {'measure': 'Change from baseline over time in visual functioning questionnaire', 'timeFrame': '1 year', 'description': 'Assessed by the Modified National Eye Institute Visual Functioning Questionnaire'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['LCA', 'Retinal Degeneration', 'IRD', 'adeno associated virus', 'gene therapy', 'LCA5'], 'conditions': ['LCA5']}, 'descriptionModule': {'briefSummary': 'The goals of this clinical trial are assess the natural course of LCA5-IRD over 6 months and to evaluate the safety and preliminary efficacy of subretinal gene therapy with OPGx-001 in patients with inherited retinal degeneration due to biallelic mutations in the LCA5 gene. Funding Source- FDA Office of Orphan Products Development (OOPD).', 'detailedDescription': 'This is a non-randomized, open-label, phase 1/2 dose-escalation study evaluating untreated patients for 6 months and with three doses of OPGx-001 for the treatment of LCA5-IRD.\n\nEnrollment will begin with a low-dose of OPGx-001 delivered via single, unilateral subretinal injection (Cohort 1) and proceed to an intermediate dose (Cohort 2) and subsequent high dose (Cohort 3). Escalation to each next cohort will proceed only after review of all data and upon recommendation by an independent data monitoring committee (IDMC).\n\nConcurrently, 16 untreated patients will be assessed for 6 months prior to treatment to study the natural course of LCA5-IRD.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '4 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Are willing and able to provide written informed consent (ICF) and, where appropriate, willing to sign an assent prior to any study procedures.\n2. Are willing to adhere to the clinical protocol and able to perform testing procedures.\n3. In part A participants must be 13 years of age or older at consent, for Part B, participants must be 4 years of age or older at consent with the ability to conduct the MLoMT.\n4. Carry disease-causing biallelic LCA5 gene mutations determined by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (historic testing up to 15 years from date of consent can be considered).\n5. Visual acuity: BCVA \\< 20/80 on the Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity chart (modified for low vision participants) in the eye to be treated\n6. Show evidence of detectable photoreceptors by Spectral Domain Optical Coherence Tomography (SD-OCT)\n7. Participant is a good candidate for surgery per investigator judgement\n8. Participant agrees to follow direction of investigator regarding restrictions post-surgery (Part A only).\n\nExclusion Criteria:\n\n1. Women who are pregnant or individuals (women of childbearing potential and men) unwilling to use effective contraception for the duration of the study, including barrier methods for the first year after investigational product (IP) administration (Part A only).\n2. Pre-existing eye conditions or complicating systemic diseases that would preclude the planned surgery. This includes individuals who are immunocompromised.\n3. History of intraocular surgery for either eye within 6 months prior to planned IP administration (Part A only).\n4. Have previously received gene therapy.\n5. Have used any investigational drug or device within 90 days or 5 estimated half-lives of treatment, whichever is longer or plan to participate in another study of drug or device during the study period.\n6. History of disease which may preclude the participant from participation, or which may interfere with outcome measure testing or test results.\n7. Incapable of performing visual function testing (e.g., FST testing) for reasons other than poor vision.\n8. Any absolute contraindication to a course of oral steroids.\n9. Any other condition that would not allow the potential participant to complete follow-up examinations during the study and, in the opinion of the Investigator, makes the potential participant unsuitable for the study.'}, 'identificationModule': {'nctId': 'NCT05616793', 'briefTitle': 'Safety and Tolerability Subretinal OPGx-001 for LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) and Non-interventional Arm With Untreated Patients', 'organization': {'class': 'INDUSTRY', 'fullName': 'Opus Genetics, Inc'}, 'officialTitle': 'An Open Label, Dose Exploration, Safety and Tolerability Study of a Subretinal Injection of an OPGx-001 Gene Vector to Participants With LCA5-Associated Inherited Retinal Degeneration (LCA5-IRD) With OCncurrent Non-Interventional Follow-Up of Untreated Patients', 'orgStudyIdInfo': {'id': 'OPGx-LCA5-1001'}, 'secondaryIdInfos': [{'id': 'FD-R-008174', 'type': 'OTHER_GRANT', 'domain': 'Funding Source- FDA Office of Orphan Product Development (OOPD) Grant'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Dose Group 1', 'description': 'A single, unilateral, subretinal injection of low dose (1E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a low dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).', 'interventionNames': ['Biological: AAV8.hLCA5']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Group 2', 'description': 'A single, unilateral, subretinal injection of an intermediate dose (3E10 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of an intermediate dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).', 'interventionNames': ['Biological: AAV8.hLCA5']}, {'type': 'EXPERIMENTAL', 'label': 'Dose Group 3', 'description': 'A single, unilateral, subretinal injection of high dose (1E11 vg/eye) OPGx-001 is injected into two LCA5 adults (18 yo or above) in a sentinel fashion. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, a subsequent LCA5 adolescent (13-17) may be treated in a sentinel fashion, with a unilateral, subretinal injection of OPGx-001. A 30-day safety evaluation and data committee review and approval of continued dosing occurs. If additional dosing is recommended, two remaining adolescents (13-17) are eligible to be treated with a single, unilateral, subretinal injection of a high dose of OPGx-001. Total cohort size is 5 (2 adults and 3 adolescents).', 'interventionNames': ['Biological: AAV8.hLCA5']}, {'type': 'NO_INTERVENTION', 'label': 'Part B Observational', 'description': 'Part B will occur concurrently with Dose Groups 1-3. Sixteen patients will be assessed for 6 months to assess the natural course of LCA5-IRD, then will be treated with OPGx-001 which will be described in a future protocol amendment.'}], 'interventions': [{'name': 'AAV8.hLCA5', 'type': 'BIOLOGICAL', 'description': 'Adeno-associated virus vector expressing human LCA5 gene', 'armGroupLabels': ['Dose Group 1', 'Dose Group 2', 'Dose Group 3']}]}, 'contactsLocationsModule': {'locations': [{'zip': '19104', 'city': 'Philadelphia', 'state': 'Pennsylvania', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Mariejel Weber', 'role': 'CONTACT', 'email': 'mariejel.weber@pennmedicine.upenn.edu', 'phone': '215-662-6396'}, {'name': 'Tomas Aleman, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'University of Pennsylvania Perelman School of Medicine', 'geoPoint': {'lat': 39.95238, 'lon': -75.16362}}, {'zip': '75231', 'city': 'Dallas', 'state': 'Texas', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Martin Klein', 'role': 'CONTACT', 'email': 'mklein@retinafoundation.org', 'phone': '214-363-3911'}, {'name': 'Mark Penessi, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'Retina Foundation of the Southwest', 'geoPoint': {'lat': 32.78306, 'lon': -96.80667}}], 'centralContacts': [{'name': 'Sarah Tuller', 'role': 'CONTACT', 'email': 'STuller@OpusGtx.com', 'phone': '8608882718'}, {'name': 'Jasminder Soto', 'role': 'CONTACT'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Opus Genetics, Inc', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'University of Pennsylvania', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}